Opium probably acts simply by an influence upon the vital properties of the tissues, without any chemical reagency whatever. Hence the long comparative impunity under its abuse. At one time I was disposed to think that its first stimulating action on the heart and brain might be owing to a sympathetic impression extended from the stomach; but the correctness of this opinion seems to me more than doubtful, now that we know how rapidly it is absorbed, and how quickly it may be conveyed with the blood to all parts of the system. That it is absorbed is proved by the fact that, in fatal cases of poisoning, it frequently happens, even when there has been no vomiting, that none of it is found in the stomach. Besides, the smell of opium is sometimes observable in the breath and excretions of persons who have taken it largely, and has been noticed in the blood. Barruel asserts that he has detected morphia in the blood and urine of a person poisoned with opium. (Pereira, Mat. Med., 3d ed., p. 2120.) The milk of nurses under its influence has produced its peculiar effects on the sucking child. When introduced into the jugular vein, it has been found to produce the same effects as when taken by the stomach. Finally, if applied to a nerve, without access to the blood-vessels, it does not act on the brain.

From its slightly stimulating effect on the surfaces with which it is observably brought into contact, it may be supposed, when in the circulation, to exercise a similar influence wherever it is carried, and thus to produce the moderate excitement of the heart which accompanies its primary operation. But its influence is felt especially by the nervous centres in the brain, and more particularly by those of the cortical portion of the cerebrum, through which the intellectual and emotional functions of the mind are probably exercised. The sensory centres, and the respiratory centre in the medulla oblongata, appear also to be specially affected. But if the cerebellum be, as supposed by Flourens, the seat of the power of combining motions, and as Gall and Spurzheim maintain, that of the sexual propensity, it probably participates little in the original stimulant impression. The operation of opium upon the nervous centres I maintain to be essentially stimulant. The primary mental excitement may thus be readily accounted for, as well as the more rapid respiration, and increased muscular power. It is not improbable that the stimulation of the heart may really proceed from a similar cause. and not from the direct contact of the opium or its active principles. But how account for the subsequent calm in all these functions, and the remarkable diminution and almost suspension which follow, as indicated by the impaired sensibility and power of motion, and the soporose condition more or less profound? Are these the result of a direct sedative or depressing influence following the stimulant? I think not. The real depression takes place long subsequently, after the direct action of the medicine has ceased. They are readily explicable upon the general doctrine of irritation, which I have maintained in this work and elsewhere. Irritation is stimulation beyond the healthy point. The two terms may be considered as synonymes in reference to our present purpose. When, then, a part is stimulated, it receives an additional supply of blood, and the supply increases with the stimulation until it ends in inflammation. Now the first effect of the blood entering the part is to supply the means for an increase of its healthy function; a larger supply interferes with the due action of the part, though the excitement may still continue; a still further quantity overwhelms it, and impairs or suspends altogether the exercise of its function. In other words, the effects of stimulation upon any part are first to augment, then to derange, and lastly to impair its function; and all this through the direct influence of the stimulant. Apply this law to the action of opium on the cerebral centres. It first moderately stimulates and moderately congests them; thus increasing their function, and giving rise to the elevated intellectual, emotional, and sensory phenomena, and perhaps to the circulatory and respiratory excitement, which characterize the early period of its operation; it continues to stimulate, and thus further congests them, and in this way occasions the disordered sounds and other sensations, and the derangement of the intellectual, emotional, and motor functions which sometimes come on at this period; it still continues to stimulate, and yet further to congest the centres, the functions of which are now diminished or suspended, causing first a sensorial calm, and ultimately sleep. If the quantity of the opium is very large, the congestion is hastened and increased with the more prompt and powerful stimulation; and hence the speedy occurrence of profound sleep or coma. The influence upon the circulation and respiration corresponds with this view. In active congestion of the brain the pulse usually becomes slower, fuller, and stronger, and the respiration slower and deeper; and thus it is in the early stage of the soporose effect of opium, showing that the sensorial phenomena proceed from a similar influence. Indeed, there is a marked resemblance between the effects of opium and a gradually increasing active congestion of the brain. In the latter, as in the former, the cerebral functions are first somewhat excited, then they are discomposed, as shown by abnormal sounds, etc., in the head, and then diminished or suppressed, as proved by the drowsiness and stupor which supervene; and the resemblance is extended, as already stated, to the respiratory and circulatory functions.

Thus far we have been attending to the direct influence of the opium.

The condition which follows is in accordance with another general pathological law, that every over-excitement must be followed by a corresponding depression. The cerebral centres, no longer stimulated by the opium, fall necessarily into a depressed state. No more blood is now attracted to them. They have not even the power of expelling the excess which has overwhelmed them. Hence, a failure of all the dependent functions, and the universal prostration that ensues.

I consider the above question as not purely theoretical, but highly practical in its bearing, and therefore important to be decided correctly. If opium is a real sedative to the nervous centres in its second and most powerful action, then it must be the great remedy in all cases of over-excitement of the brain, from slight vascular irritation of that organ up to apoplectic congestion, and even inflammation; for the sedative influence would vastly overbalance the stimulant, especially if the medicine should be given largely, and would thus produce much more good than harm. But every experienced practitioner knows that these are exactly the conditions in which opium is calculated to do harm. If, on the contrary, it be altogether a stimulant to the brain throughout its direct action, whether during the excitement or suppression of the cerebral functions, then it is contraindicated in the conditions just referred to, and would be most appropriate in all cases of functional depression or debility of the brain; and this is really the case. Upon the principle here stated, opium may be prescribed rationally; upon the other, that, namely, which considers it sedative to the brain, it must be given empirically.

But another important point, in reference to therapeutics, is that, while opium is a powerful cerebral stimulant, it operates really as a sedative upon many of the functions and organs of the body, which are sustained in their due state by influence from the nervous centres. By the overstimulation of these centres, it disables them from extending their proper influence to other organs, and thus acts as a positive, though indirect sedative to the latter. Hence, opium may often be prescribed with great advantage as a sedative in various disordered conditions of the system, provided the brain be either sound, so as not to be materially injured by its action, or depressed, so as to be benefited by it, Under the therapeutic head, there will be frequent opportunities of illustrating the principle here laid down.

It is highly probable that, upon all the nervous centres, those of the spinal marrow and the sympathetic ganglia, for example, and upon all the force-generating nervous matter as distinguished from the mere conveying structure, wherever it may exist, opium acts in the same manner as upon the brain, though in a less degree. Sufficient investigation, however, has not been made upon this point, to justify a positive conclusion.